Chemistry and Chemical Biology ETDs

Publication Date

9-7-1973

Abstract

A new general synthetic sequence and cyclization method was developed which utilizes parts of both the Reissert and Madelung indole cyclization methods and leads to substituted pyrrolo[2,3-d]pyridazines,pyrrolo[3,2-c]-pyridazines, and pyrrolo[2,3-c]pyridazines. Thus, ethyl pyridazinylpyruvatel-oxides substituted with an ethyl formimidate or acetimidate group adjacent to the pyruvate group provides immediate precursors to pyrrolopyridazines. Mild acid hydrolysis of the acylimidate and subsequent cyclodehydration. Parallel to the latter stage of the Reissert indole cyclization method, affords ethyl pyrrolopyridazine carboxylates in high yields. On the other hand, treatment of the acylimidates with base provided ethyl pyrrolopyridazine glyxalates in high yields in a manner similar to the Madelung indle cyclization method. The placement of the acylimidate group with respect to the N-oxide function and the use of either a formimidate or an acetimidate group affects the synthetic sequences and the cyclization reaction.

The resulting substituted pyrrolopyridazines were allowed to react further to gain an insight into the reactivity of these ring systems as well as provide a number of pyrrolopyridazines with potential biological activity. Several of the resulting pyrrolopyridazines were converted to compounds which resemble the natural occurring purines and would be good candidates for glycosidation reactions.

The pyrrolo[3,2-c]pyridazine ring systems which was synthesized by this cyclization method represents a novel heterocyclic ring system.

Several new pyridazino[4,5-c]pyridazines and a number of new pyridazine intermediates leading to the synthesis of the pyridazino[3,4-c]pyridazine and pyridazino[4,3-c]pyridazine ring systems were prepared.

A review of all pyrrolopyridazines contained in the chemical literature up to July, 1973 is presented.

Language

English

Document Type

Dissertation

Degree Name

Chemistry

Level of Degree

Doctoral

Department Name

Department of Chemistry and Chemical Biology

First Committee Member (Chair)

Raymond N. Castle

Second Committee Member

Illegible

Third Committee Member

James Francis Barbour

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